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Project
The role of the epiplayer RBBP4 in malignant progression and relapse in multiple myeloma. (FWOSB137)
Multiple myeloma (MM) is the second most common blood cancer
located in the bone marrow. MM remains incurable, as most patients
in remission develop a tumor that is resistant to all drugs. Epigenetic
defects play a major role in MM, by promoting aggressiveness, drug
resistance and disease progression. Targeting the enzymes
responsible for these epigenetic changes (the epiplayers) holds
promise to delay/overcome relapse, but the knowledge-gap in which
epiplayers are key in driving MM progression and relapse and the
lack of selective inhibitors severely hampers clinical implementation.
Recently, within the HEIM lab we found that one epiplayer, namely
retinoblastoma binding protein 4 (RBBP4), is upregulated in
malignant plasma cells of relapsed patients, indicating that RBBP4
could play an important role in MM progression and relapse. Here, I
aim to 1) characterize the role of RBBP4 in MM cell biology, drug
response and malignant progression, 2) identify the underlying
mechanisms of action and 3) develop a first, exosome-based RBBP4
-specific targeting tool to evaluate its potential as therapeutic target.
To achieve this, we will use complementary in vitro and in vivo MM
models. In the short-term, this project will reveal for the first time the
function and therapeutic potential of RBBP4 in MM. In the long-term,
it will help to design new, RBBP4-based therapies to counter drug
resistance
located in the bone marrow. MM remains incurable, as most patients
in remission develop a tumor that is resistant to all drugs. Epigenetic
defects play a major role in MM, by promoting aggressiveness, drug
resistance and disease progression. Targeting the enzymes
responsible for these epigenetic changes (the epiplayers) holds
promise to delay/overcome relapse, but the knowledge-gap in which
epiplayers are key in driving MM progression and relapse and the
lack of selective inhibitors severely hampers clinical implementation.
Recently, within the HEIM lab we found that one epiplayer, namely
retinoblastoma binding protein 4 (RBBP4), is upregulated in
malignant plasma cells of relapsed patients, indicating that RBBP4
could play an important role in MM progression and relapse. Here, I
aim to 1) characterize the role of RBBP4 in MM cell biology, drug
response and malignant progression, 2) identify the underlying
mechanisms of action and 3) develop a first, exosome-based RBBP4
-specific targeting tool to evaluate its potential as therapeutic target.
To achieve this, we will use complementary in vitro and in vivo MM
models. In the short-term, this project will reveal for the first time the
function and therapeutic potential of RBBP4 in MM. In the long-term,
it will help to design new, RBBP4-based therapies to counter drug
resistance
Date:1 Nov 2022 → Today
Keywords:Multiple myeloma, retinoblastoma binding protein 4 (RBBP4), exosome-based RBBP4 specific targeting tool
Disciplines:Hematology, Cell death, Epigenetics, Cancer biology, Cancer therapy